A Systems Approach to Characterizing and Predicting Thyroid Toxicity Using an Amphibian Model
EPA has been mandated to evaluate the potential effects of chemicals for disruption of the estrogen, androgen, and thyroid hormone axes. The objective of this project is to develop a hypothalamic-pituitary-thyroid (HPT) model capable of integrating data from different levels of biological organization into a coherent system. This model will provide a rational framework to organize and interpret toxicological data from the molecular to the organismal levels and will serve as a basis for development of predictive tools related to thyroid toxicity. To develop this model, experiments are being conducted to better understand the relationships of the critical sub-components of the system. These experiments include development of in vitro and ex vivo assay systems to measure gene expression, hormone production, and other endpoints integral to the control of thyroid hormone. These endpoints in the pituitary, thyroid, and peripheral tissues are being measured under normal conditions and following exposure to chemicals known to interfere with TH synthesis. The molecular and cellular changes linked with functional measurements of key hormones and enzymes that are part of the HPT pathway, will all be interpreted in the context of organismal-level effects. The primary benefit of this work is to develop a sufficient understanding of the HPT so that predictive models can be developed, testing protocols can be abbreviated, and efforts in inter-species extrapolation can be improved.
Inhibition of Thyroid Release from Cultured Amphibian Thyroid Glands - Hornung et al., 2010 (in review)
Research project update date
March 22, 2010